Smuggling across the Border: How Arthropod-Borne Pathogens Evade and Exploit the Host Defense System of the Skin

Bernard, Quentin; Jaulhac, B.; Boulanger, Nathalie

doi:10.1038/jid.2014.36

Cited by 30 publications

(27 citation statements)

References 134 publications

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“…Pathogen transmission occurs during the uptake of a blood meal, when ticks inject saliva into the mammalian host, affecting hemostasis and host immune responses (1)(2)(3). Tick saliva contains an arsenal of molecules with antihemostatic, anesthetic, and anti-inflammatory properties (4)(5)(6). How tick salivary proteins manipulate the activity of the inflammasome remains mostly elusive.…”

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confidence: 99%

The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated Inflammasome Activation

et al. 2016

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i Tick saliva contains a number of effector molecules that inhibit host immunity and facilitate pathogen transmission. How tick proteins regulate immune signaling, however, is incompletely understood. Here, we describe that loop 2 of sialostatin L2, an anti-inflammatory tick protein, binds to annexin A2 and impairs the formation of the NLRC4 inflammasome during infection with the rickettsial agent Anaplasma phagocytophilum. Macrophages deficient in annexin A2 secreted significantly smaller amounts of interleukin-1␤ (IL-1␤) and IL-18 and had a defect in NLRC4 inflammasome oligomerization and caspase-1 activation. Accordingly, Annexin a2-deficient mice were more susceptible to A. phagocytophilum infection and showed splenomegaly, thrombocytopenia, and monocytopenia. Providing translational support to our findings, better binding of annexin A2 to sialostatin L2 in sera from 21 out of 23 infected patients than in sera from control individuals was also demonstrated. Overall, we establish a unique mode of inflammasome evasion by a pathogen, centered on a blood-feeding arthropod.

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confidence: 99%

The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated Inflammasome Activation

et al. 2016

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“…In arthropod-borne diseases, the skin constitutes a key interface where pathogens are inoculated and can persist (31,32). Local cutaneous manifestations are often the first clinical signs to appear before dissemination to extracutaneous sites occurs (3).…”

Section: Discussionmentioning

confidence: 99%

Discovery and Targeted Proteomics on Cutaneous Biopsies Infected by Borrelia to Investigate Lyme Disease*

Schnell

Bœuf

Westermann

et al. 2015

Molecular & Cellular Proteomics

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Lyme disease is the most important vector-borne disease in the Northern hemisphere and represents a major public health challenge with insufficient means of reliable diagnosis. Skin is rarely investigated in proteomics but constitutes in the case of Lyme disease the key interface where the pathogens can enter, persist, and multiply. Therefore, we investigated proteomics on skin samples to detect Borrelia proteins directly in cutaneous biopsies in a robust and specific way. We first set up a discovery gel prefractionation-LC-MS/MS approach on a murine model infected by Borrelia burgdorferi sensu stricto that allowed the identification of 25 Borrelia proteins among more than 1300 mouse proteins. Then we developed a targeted gel prefractionation-LC-selected reaction monitoring (SRM) assay to detect 9/33 Borrelia proteins/peptides in mouse skin tissue samples using heavy labeled synthetic peptides. We successfully transferred this assay from the mouse model to human skin biopsies (naturally infected by Borrelia), and we were able to detect two Borrelia proteins: OspC and flagellin. Considering the extreme variability of OspC, we developed an extended SRM assay to target a large set of variants. This assay afforded the detection of nine peptides belonging to either OspC or flagellin in human skin biopsies. We further shortened the sample preparation and showed that Borrelia is detectable in mouse and human skin biopsies by directly using a liquid digestion followed by LC-SRM analysis without any prefractionation. This study thus shows that a targeted SRM approach is a promising tool for the early direct diagnosis of Lyme disease with high sensitivity (<10 fmol of OspC/mg of human skin biopsy). Molecular & Cellular Proteomics

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“…Lors de la piqûre de tique et de l'inoculation de la bactérie, le patient ne ressent rien en général, compte tenu de l'activité anesthésiante de la salive, excepté parfois chez certaines personnes régulièrement exposés aux piqûres, qui ont développé une hypersensibilité à la salive de tique. La peau étant une interface essentielle dans les maladies à transmission vectorielle, elle joue, par son immunité, un rôle clef dans le développement ultérieur ou le contrôle de l'infection (Bernard et al 2014). Chez la plupart des patients (80% environ), le premier et le plus fréquent des signes cliniques est l'apparition d'une lésion cutanée, appelée érythème migrant (EM) : manifestation cardinale de la maladie.…”

Section: Manifestations Cliniquesunclassified

Borréliose de Lyme : impact de l’homme sur la persistance et la circulation de Borrelia Burgdorferi sensu lato dans l’environnement

Boulanger¹,

Jaulhac²

2015

bavf

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La borréliose de Lyme est une infection bactérienne transmise par les tiques dures du genre Ixodes. C'est avant tout une zoonose qui circule dans un large panel d'hôtes vertébrés sauvages (lézards, oiseaux, rongeurs, cervidés…) et domestiques ; l'homme est un hôte accidentel. Ces dernières années, la notion d'émergence a été évoquée pour cette pathologie, notamment à cause des modifications climatiques. Les raisons sont plus complexes. La pathologie est mieux connue sur un plan médical grâce aux progrès diagnostiques, cliniques et épidémiologiques. De plus, l'analyse des différents facteurs biotiques et abiotiques laissent penser que l'anthropisation des environnements où évoluent les tiques, est responsable de l'émergence des maladies transmises par les tiques dont la borréliose de Lyme. En effet, l'homme modifie pour des raisons socio-économiques surtout, les écosystèmes forestiers et la faune sauvage qui favorisent le développement des populations de tique et donc des maladies qu'elles transmettent. Mots

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Smuggling across the Border: How Arthropod-Borne Pathogens Evade and Exploit the Host Defense System of the Skin

Cited by 30 publications

References 134 publications

The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated Inflammasome Activation

The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated Inflammasome Activation

Discovery and Targeted Proteomics on Cutaneous Biopsies Infected by Borrelia to Investigate Lyme Disease*

Borréliose de Lyme : impact de l’homme sur la persistance et la circulation de Borrelia Burgdorferi sensu lato dans l’environnement

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